Changsheng Fang, Dayang Wang, T. Campbell Arnold +2eess.IV cs.CV
Perceptual losses are widely used in medical image synthesis because they encourage agreement in high-level structure beyond voxel-wise intensity similarity. In practice, most perceptual losses are still computed with natural-image backbones such as VGG16 or ResNet50, even when the target domain is magnetic resonance imaging (MRI). This mismatch may weaken supervision for anatomy, contrast enhancement, and acquisition variability. We test whether medical foundation model features provide a more suitable perceptual loss for brain MRI contrast dose simulation. The study has two stages. First, we compare RadImageNet, SegVol, and BrainIAC with ImageNet-pretrained VGG16 and ResNet50 as frozen feature extractors on four public medical imaging benchmarks: thyroid ultrasound, breast ultrasound, anterior cruciate ligament knee MRI, and meniscus knee MRI. RadImageNet achieves the lowest mean rank across the Stage I representation suite and is selected as $φ^\star$. Second, we replace only the VGG16 feature extractor in an existing iterative brain MRI dose simulation framework with $φ^\star$. The generator, reconstruction loss, adversarial loss, auxiliary losses, optimization schedule, and loss weights are kept unchanged. Standard metrics change modestly, with PSNR increasing from 41.63 to 41.74, SSIM from 0.9739 to 0.9754, RMSE decreasing from 0.1384 to 0.1369, and residual-uptake CNR from 0.0085 to 0.0082. The visual results show the main effect: RadImageNet reduces residual enhancement in marked structures, follows a more faithful dose-reduction trajectory, and remains close to the acquired 10% low-dose target. These results support domain-aligned radiology features as a practical perceptual feature space for MRI dose simulation, while leaving clinical equivalence and larger-cohort validation as future work.
Dynamic contrast-enhanced breast MRI is central to cancer diagnosis and monitoring, but requires gadolinium-based contrast agents. In this work, we address pre-to-post contrast breast MRI synthesis for the MAMA-SYNTH challenge. We propose MAMA-FLUX.2, a conditional latent flow-matching approach based on FLUX.2-Klein-4B. The pre-contrast image is encoded as spatial conditioning, while the model predicts the flow field associated with the post-contrast target latent. To adapt the pretrained model efficiently, we use LoRA fine-tuning and introduce a regional training objective combining global flow matching, tumor-region supervision, and stable foreground regularization. We further investigate LoRA rank, intensity windowing, and regional loss weights on axial slices, prioritizing clinically relevant tumor-focused metrics. Our ablation study shows that moderate tumor and stable-foreground weighting improves the trade-off between image fidelity and tumor-region accuracy. The final model achieves the best overall balance with LoRA rank/$α=64/64$, $\mathrm{MHA}_{\max}=25$, $λ_{\mathrm{tumor}}=0.25$, and $λ_{\mathrm{stable}}=0.1$. These results demonstrate that compact pretrained rectified-flow transformers can be adapted for contrast-enhanced MRI synthesis using parameter-efficient fine-tuning and task-aware regional losses.
Marc Rodríguez, Grzegorz Skorupko, Nay Aung +3cs.CV cs.AI
Synthetic image generation is a promising strategy to address data scarcity and the underrepresentation of clinically important phenotypes in medical imaging, yet generating images that faithfully reflect meaningful patient characteristics remains challenging. In this work, we investigate metadata-conditioned cardiac magnetic resonance (CMR) synthesis using a pretrained latent diffusion model, encoding structured clinical metadata and slice position as textual prompts to guide CMR generation. To improve metadata adherence and address the imbalance of clinical attributes, we integrate three strategies: Metadata-Free Classifier-Free Guidance (CFG), Contrastive Batching, and Inverse-Frequency Sampling. The framework was fine-tuned and evaluated on 59,058 short-axis CMR from the UK Biobank using paired image similarity, distributional fidelity, and subgroup-level analyses. The combined approach achieved a Fréchet Inception Distance (FID) of 37.47, improving by 57.04\% over the same model fine-tuned without these strategies and by 28.68\% over a previous text-conditioned CMR diffusion baseline requiring cardiac geometry as additional input, while relying solely on patient metadata. This distributional gain, driven mainly by Metadata-Free CFG, came with a modest reduction in paired similarity, suggesting that the model prioritizes population-level realism over exact image reproduction. Subgroup analyses demonstrated improved alignment across demographic and acquisition-related metadata, with disease-specific conditioning being the most challenging task. These findings demonstrate the potential of generative foundation models for clinically meaningful CMR synthesis while highlighting the need for more effective metadata-aware conditioning strategies. Our code is available at https://github.com/rodriguezmarc/conditional-cmr.
Rashmi Bhaskara, Waleed M. Almutairi, Matthew Gopaulchan +5cs.CV physics.med-ph
Deep learning models that synthesize PET from CT or MRI can reduce patient dose and scanner demand, but are typically optimized with global losses such as L1 or mean squared error (MSE) that treat all voxels similarly. In whole-body PSMA-PET, tumor voxels occupy only a small fraction of the volume, yet carry the clinically relevant activity signal; as a result, models can achieve high structural similarity index measure (SSIM) and peak signal-to-noise ratio (PSNR) while still underestimating lesion activity or failing to preserve tumor-specific structure. Radiomics provides biologically meaningful descriptors of tumor intensity and texture, but direct radiomics conditioning is time-consuming because it requires feature extraction from delineated lesion regions. We propose LAFNO, a Lesion-Aware Adaptive Fourier Neural Operator for CT-to-PSMA-PET synthesis that replaces high-dimensional radiomics conditioning with two efficient CT-derived proxy channels. Motivated by radiomics analysis of PSMA-avid tumor core and peritumoral regions, LAFNO uses a contrast proxy for local density variation and a disorder proxy for local texture heterogeneity, both injected into the model bottleneck. LAFNO combines whole-volume reconstruction with lesion-level total lesion activity (TLA), tumor-core contrast, and peritumoral supervision. We evaluated LAFNO against four baseline architectures on the TCIA PSMA-PET-CT-Lesions dataset. LAFNO remained competitive on whole-volume image quality, achieving SSIM of 0.960 and 0.938 for 18F- and 68Ga-PSMA, respectively, while reducing per-patient TLA error to 48.3% and 64.0% for 18F- and 68Ga-PSMA, respectively, and achieving the highest tumor-core radiomics reproducibility across all feature classes for both tracers. Peritumoral reproducibility remained tracer-dependent, indicating that biological fidelity in synthetic PSMA-PET remains challenging.
Magnetic field strength is a major source of domain shift in magnetic resonance imaging (MRI), affecting signal-to-noise ratio, tissue contrast, spatial detail, and the visibility of anatomical boundaries. The MRIxFields 2026 challenge investigates this problem through cross-field MRI translation across acquisitions at 0.1T, 1.5T, 3T, 5T, and 7T. Its three tasks, Any-to-7T, 0.1T-to-High, and Any-to-Any synthesis, require the generation of target-field image characteristics while preserving subject-specific anatomy. This problem is particularly challenging because paired acquisitions of the same subject across multiple field strengths are rarely available for training. We propose a 3D unpaired cross-field MRI translation framework based on field-conditioned content-style pretraining. The proposed framework first learns controllable field-to-field translation across all available field strengths by disentangling anatomical content from field-dependent contrast characteristics. The pretrained backbone is then adapted to task-specific target domains. Our model comprises a 3D content encoder, a 3D style encoder, a field-conditioned style generator, an AdaIN-modulated decoder, and a multi-field discriminator. Adversarial learning encourages realistic target-field appearance, while cycle-consistency, identity, content, style, and diversity constraints promote anatomical fidelity and controllable translation. We evaluate the proposed method on MRIxFields data spanning five field strengths and three MRI modalities. Experiments on paired test data demonstrate that the framework can adapt to the three challenge settings while preserving three-dimensional anatomical structure in the synthesized volumes. The implementation code is publicly available at https://github.com/Idea89560041/3D-MRI-Field-Translation.
Sina Amirrajab, Zohaib Salahuddin, Henry C Woodruff +1eess.IV cs.CV
Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is central to breast cancer imaging, but gadolinium administration increases scan burden and motivates contrast-reduced alternatives, including synthetic contrast generation. We propose a latent bridge matching (LBM) framework for synthesizing peak-enhanced breast DCE-MRI from pre-contrast images in the MAMA-SYNTH challenge setting. Instead of starting from Gaussian noise as in conventional latent diffusion models (LDMs), the proposed model learns a conditional bridge between paired pre-contrast and peak-enhanced VAE latents. A latent UNet predicts the remaining correction from intermediate bridge states to the peak-enhanced latent, enabling iterative refinement while keeping the trajectory anchored to patient-specific anatomy. We evaluated two LBM conditioning variants on 91 DUKE validation cases. For the tumor-conditioned variant, tumor masks were used as conditioning inputs. Tumor-conditioning improved performance compared with pre-contrast conditioning, reducing MSE from 1.023 to 0.940 and FRD from 7.523 to 4.716, while increasing tumor SSIM from 0.355 to 0.429. The tumor-conditioned LBM also outperformed the evaluated LDM baseline on this validation cohort. These results suggest that latent bridge matching is a promising pre-contrast-anchored formulation for virtual contrast enhancement, while further work is needed to validate generalization and remove dependence on ground-truth tumor masks at inference.
Robin Trombetta, Carole Lartiziencs.CV cs.LG eess.IV
The development of deep learning over the past decade has revolutionized medical imaging segmentation, allowing the extraction of precise descriptors from large volumes to characterize pathologies. Data augmentation is a technique widely regarded as a way to improve model training. It includes simple transformations like spatial operations or intensity modifications, but also more advanced synthesis techniques. Their goal is to generate new realistic samples from an existing dataset to diversify the images used during training. Among them, several propose different mixing strategies to combine real samples. However, one of their major shortcomings is to yield limited variability in terms of generated lesion shapes and locations. In this work, we introduce a novel image synthesis method, called OTLesMix, that leverages Wasserstein barycenter and optimal transport plan to generate realistic and diverse samples. We evaluated our method on three brain lesion segmentation tasks, on which it improves the Dice score compared to a model trained without synthetic data by 2.9 to 6.6 points, and outperforms state-of-the-art mix-based methods.
Harvey Mannering, Yilin Zhang, Ziao Liu +3eess.IV cs.CV cs.LG physics.med-ph
Prenatal ultrasound imaging is key for assessing fetal health, but AI progress is limited by scarce, privacy-restricted, and hard-to-annotate datasets. We propose a high-resolution fetal ultrasound synthesis framework based on the EDM2 diffusion architecture, trained on multiple public datasets to generate 512x512 images across six anatomical classes. Our method achieved improved image quality with lower FID scores and enhanced downstream fetal plane classification, reaching 93.36% ensemble accuracy after fine-tuning, surpassing real-data-only training. Clinical evaluation by an experienced fetal ultrasound specialist (10+ years) on 100 images yielded a mean realism score of 2.67/5, with real images rated higher than synthetic. Artefacts included smoothing, speckle irregularities, and anatomical inconsistencies. Code, data, models and other resources to reproduce this work are available at https://github.com/xfetus/fetal-ultrasound-edm2.
Virtual contrast enhancement (VCE) synthesizes enhanced breast MR images from pre-contrast acquisitions. Modern latent generators offer strong image priors, but their bounded natural-image autoencoders conflict with the non-canonical intensity scale of MRI. We show that the upper bound can alter radiomic fidelity before generation, while scaling source and target independently creates a coordinate inconsistency. We propose Predictive Enhancement Calibration (PEC), which represents each pair in a shared, case-adaptive coordinate during training and predicts its unavailable upper endpoint from the pre-contrast image at inference. We integrate PEC with a pretrained FLUX latent flow transformer via parameter-efficient reference conditioning. Target round trips first isolate representation loss before generation; near-matched conditional models then compare PEC with fixed-wide and separate coordinates under comparable training budgets and backbone settings. On the fixed internal MAMA100 development cohort, PEC improves all eight point estimates in this source-only VCE setting, with paired evidence strongest for MSE and LPIPS.\noindent\textbf{Code:} https://github.com/tanlei0/pec-breast-mri-vce
Mohd Maaz Khan, Oluwaseyi Oderindephysics.med-ph cs.CV
18F-FDG PET/CT plays a central role in staging, treatment planning, and response assessment for head and neck cancer by providing functional information that complements anatomical CT imaging. However, PET acquisition requires radiotracer administration, specialized infrastructure, and additional cost, limiting its availability for repeated imaging. We present a proof of concept deep learning framework for synthesizing PET like images directly from routine CT scans with the goal of providing complementary metabolic information that may support imaging triage and clinical decision support rather than replace diagnostic PET. Forty-four patients from the publicly available QIN-HEADNECK dataset were retrospectively analyzed using five fold cross-validation. We propose a fully three dimensional dual path architecture consisting of (i) a regression U-Net optimized for voxel-wise quantitative SUV estimation and (ii) a conditional generative adversarial network optimized for realistic PET texture. Their outputs are integrated using hotspot guided Laplacian pyramid blending, allowing quantitative information from the regression pathway to be preserved within metabolically active regions while leveraging adversarial texture synthesis elsewhere. The proposed framework achieved a mean absolute error of 0.00395, PSNR of 39.19 dB, and SSIM of 0.9634 on reconstructed three dimensional PET volumes. Qualitative evaluation demonstrated accurate localization of many FDG-avid lesions while producing anatomically realistic background texture. Consistent with previous CT to PET synthesis studies, the principal limitation was systematic underestimation of SUV within highly metabolically active tumor regions.
Andrea Borghesi, Xin Wang, Jonas Teuwen +1eess.IV cs.AI cs.LG
Inferring contrast enhancement from one pre-contrast breast MRI slice is underdetermined: post-contrast appearance contains physiological information that is not uniquely encoded in baseline anatomy. Optimizing only paired pixel fidelity can suppress uncertain lesion enhancement, whereas adversarial or stochastic generative objectives can favor realistic post-contrast appearance without guaranteeing patient-specific lesion fidelity. We introduce MIRAGE, a residual 2D U-Net that combines global reconstruction and perceptual losses with three forms of lesion-aware supervision available only during training: an asymmetric penalty for missed tumor enhancement, multi-scale auxiliary tumor segmentation, and guidance through a frozen post-contrast tumor segmentation nnU-Net. We evaluate the method on 301 cases from the multi-centre MAMA-SYNTH data using eight complementary image-, region-, radiomics-, and segmentation-based metrics. MIRAGE ranks first on six metrics and markedly improves downstream lesion localization over tuned pix2pix, conditional diffusion, and latent bridge-matching baselines. The generative alternatives retain advantages in LPIPS or contrast classification, revealing a clear fidelity-utility trade-off. Leave-one-in and leave-one-out ablations show that the losses are partly redundant for lesion localization but exert distinct effects on appearance, radiomics, and boundary accuracy. These results support task-aware synthesis while also showing that its apparent optimality is conditional on the downstream models and metrics used to define utility.
The diagnosis of spinal diseases is often assisted by 3D imaging techniques in clinical practice. However, precise 3D spinal assessment is limited by the high costs of 3D imaging hardware and the challenges posed by the physical differences between imaging modalities, which hinder the generalizability of models. To address these issues, we propose UniSpine-GS, an efficient, physics-aware Gaussian framework designed for novel-view projection rendering in multi-view spine imaging via a 3D-aware representation. Instead of performing explicit 3D reconstruction, our approach learns a geometry-aware Gaussian representation that ensures anatomical consistency across different views. We introduce SPWM, a structure-guided loss reweighting strategy to improve boundary fidelity and local details. We evaluate our method on the CTSpine3D dataset and a newly constructed 3D fetal ultrasound dataset, FeSpine3D. Our results demonstrate that UniSpine-GS significantly outperforms existing methods across all metrics, offering a practical and cost-effective solution for unified multi-view medical imaging. Our code is publicly available at https://github.com/orangeisland66/UniSpine-GS.
Yuexi Du, Leya Barrientos, Laura Sheiman +3cs.CV cs.AI cs.LG
Multiview mammography relies on paired craniocaudal (CC) and mediolateral oblique (MLO) views to provide complementary projections of a 3D breast volume, enabling precise anomaly localization. However, acquiring high-quality, balanced datasets remains challenging for deep learning applications. We propose a novel method to synthesize multiview mammograms by leveraging the inherent geometric relationship between CC and MLO views. To enforce an implicit 3D consistency prior during generation, we develop an alignment module that searches a 2D affine transformation subspace to establish optimal anatomical correspondence. Leveraging this alignment, we introduce a pixel-space self-consistency loss based on the Earth Mover's Distance (EMD) between the 1D anteroposterior (AP) axis tissue distributions of the generated images. Integrated into a pretrained flow matching model, MammoFlow forces synthesized pairs to share physically plausible tissue distributions from the chest wall to the nipple. To our knowledge, this is the first work to guide multiview mammogram generation using implicit geometric tissue correspondence. Our method demonstrates superior image quality, passes expert radiologist evaluation, and generates physically consistent pairs that improve downstream classification AUC by 5%. Code is available at https://github.com/XYPB/MammoFlow
Cross-domain diagnosis remains a major challenge in cervical cell pathology due to pronounced domain shifts across institutions and the subtle visual differences among disease stages, which jointly impair model generalization. To address these issues, this paper proposes a two-stage framework for cross-domain cervical cell detection. In the first stage, we propose the Spatially-Continuous Unpaired Neural Schrödinger Bridge (SC-UNSB), which constructs a synthetic intermediate domain to mitigate cross-domain distribution shifts by modeling image translation as an entropy-regularized optimal transport process. In the second stage, we propose a dual-level feature alignment strategy within a knowledge distillation, which progressively aligns shallow structural features and deep semantic representations to facilitate the transfer of domain-invariant knowledge from the source to the target model. Experimental results demonstrate that the proposed method effectively mitigates domain shift and category ambiguity, improving the cross-domain detection performance.
Fabio De Sousa Ribeiro, Emma A. M. Stanley, Charles Jones +7cs.CV cs.AI cs.LG
We introduce the first generative foundation model for chest radiograph synthesis trained from scratch at the billion-parameter scale. Existing radiographic AI models often suffer from poor generalisation across patient subpopulations, institutions, and acquisition settings, resulting in limited real-world clinical utility. Controlled, high-fidelity synthesis of chest radiographs is a promising path toward diversifying clinical datasets and evaluating the robustness of diagnostic models. Therefore, we present the largest specialist generative foundation model for chest radiographs to date, with over 1.3B parameters, trained for 1.6T tokens on a curated, heterogeneous dataset comprising 1.2M radiographs and clinical expert-guided metadata. Our model supports controllable radiograph generation and editing across multiple demographic subgroups, acquisition views, and a dozen pathologies. Moreover, we significantly advance the state of the art in radiograph synthesis fidelity, producing images that are indistinguishable from real radiographs to clinical experts.
Fundus fluorescein angiography (FFA) is critical for assessing retinal vascular abnormalities, but its acquisition is invasive and not always feasible. In contrast, color fundus photography (CFP) is non-invasive and widely accessible, which has motivated studies on CFP-to-FFA synthesis. However, prior works rely solely on CFP surface texture, fundamentally limiting the ability to reconstruct functional vascular information and subtle pathological changes. To address this, we propose a novel framework that synthesizes FFA from CFP with structural guidance provided by optical coherence tomography (OCT). We construct a multi-modal retinal imaging dataset with paired CFP, FFA, and OCT from 3,676 patient eyes--the first tri-modally aligned dataset in retinal imaging. To bridge the spatial gap between OCT and fundus modalities, we propose a Spatially Aligned Cross-Modal Fusion (SACMF) module that projects depth-resolved OCT features onto the fundus plane and injects them into the CFP encoder via adaptive layer normalization. Beyond feature fusion, we further introduce Token-wise Cross-Modality Alignment (TCMA), a token-level contrastive learning strategy that explicitly aligns CFP and FFA representations at corresponding spatial positions. Our method achieves superior synthesis performance compared to state-of-the-art methods. Moreover, extensive experiments demonstrate that the FFA images synthesized by our approach bring greater improvements in downstream disease diagnosis performance than existing methods, highlighting the clinical potential of our approach as a non-invasive decision-support tool in routine workflows. The code is available at https://github.com/while-plus/OCT-guide-FFA-Syn.
Gabriel Steele, Alzahra Altalib, Alessandro Perellics.CV cs.AI physics.med-ph
We present a Dual-Domain Equivariant Generative Adversarial Network (DDE-GAN) for multimodal CT-PET image synthesis. Traditional GAN-based approaches often operate solely in the spatial domain and ignore geometric consistency, resulting in limited structural fidelity. DDE-GAN addresses these challenges by jointly learning from both spatial and frequency (Fourier) domains, capturing complementary anatomical and spectral information. Furthermore, rotational equivariance embedded in the physics of the CT and PET measurements are integrated into the loss of both the generator and discriminator to ensure consistent responses under rotations, improving anatomical accuracy. A hierarchical dual-domain training strategy enforces intra- and inter-domain consistency through multi-stage loss functions. Evaluated on the HECKTOR 2022 CT-PET dataset, DDE-GAN achieves superior synthesis quality over baseline models for CT-PET image synthesis. The results demonstrate that combining dual-domain learning with geometric equivariance substantially enhances multimodal image synthesis accuracy and robustness, enabling practical applications in PET completion and data augmentation.
Multi-contrast brain MRI provide complementary soft-tissue characteristics that aid in the screening and diagnosis of diseases. However, limited scanning time, image corruption and various imaging protocols often result in incomplete multi-contrast images. While current approaches excel in image synthesis, they often struggle to synthesize critical tumor regions and exploit contextual information in multi-contrast brain MRI effectively. To address this issue, we propose a synthesis-centric, segmentation-assisted closed-loop framework with retrieval augmentation synthesis. Our method overall takes a generative adversarial architecture, which aims to synthesize missing contrasts from any combination of available ones with a single model. To explicitly capture tumor semantics and focus synthesis on tumor regions, we add an auxiliary segmentation branch that predicts tumor masks and feeds them back as semantic conditioning in synthesis branch, thereby learning tumor-aware representations in the model and improving synthesis fidelity. Furthermore, we propose a dual-bank retrieval augmentation strategy. It dynamically queries two external knowledge bases, namely a tumor masks memory bank for crucial tumor context and cross-image contrast feature memory bank for global style information, to augment synthesis. Verified on two public multi-contrast magnetic resonance brain datasets: BraTs2020 and UCSF-BMSR, the proposed method is effective in handling medical brain images synthesis tasks and shows superior performance compared to previous methods. Code is available at:https://github.com/iBizzard/SSCF.git
Santiago Cepeda, Olga Esteban-Sinovas, Ignacio Arrese +1cs.CV cs.LG
Maximal safe resection is the primary objective in glioma surgery. Neuronavigation guidance is progressively degraded by brain shift after dural opening. Intraoperative MRI can compensate but needs dedicated infrastructure and is rarely available, whereas intraoperative ultrasound (ioUS) is inexpensive, repeatable, and compatible with routine workflows. Navigation systems combining ioUS with preoperative MRI usually rely on rigid registration; even deformable multimodal registration is limited by ultrasound speckle contrast, a narrow field of view, and the inability to represent structures absent from the preoperative scan, most critically the resection cavity and residual tumor. We propose an end-to-end pipeline that generates a new whole-brain MRI volume in the preoperative imaging space by merging the preoperative MRI, a synthetic MRI generated from the ioUS, and a deformable registration anchored on that synthetic image. It integrates a 2.5D residual-transformer synthesis backbone (ResViT-2.5D) and a two-stage registration coupling NiftyReg with a synthesis-anchored SynthMorph stage, operating directly on raw scanner inputs. On a post-resection ReMIND cohort, ResViT-2.5D produced synthetic images closely matching the intraoperative T2 across structural, intensity, and perceptual metrics. In 14 subjects with 215 expert landmarks, the synthesis-anchored registration reduced the mean target registration error from 6.27 to 5.86 mm, matching a strong classical NiftyReg baseline (5.85 mm) while yielding a diffeomorphic deformation field in every subject. The contribution is not a gain in registration accuracy but the integrated volume itself, which inside the ultrasound field of view it reflects the intraoperative post-resection state. This provides the surgeon with an MRI-like update of the operative field with potential for integration into surgical-navigation workflows.
Immunohistochemistry (IHC)is frequently used to resolve diagnostically ambiguous prostate cancer biopsy findings on hematoxylin and eosin (H&E)-stained tissue. However, PIN-4 IHC staining is typically performed on adjacent tissue sections, limiting direct spatial comparison between the H&E morphology and the corresponding immunophenotypic signal. A paired, registered H&E/PIN-4 dataset was constructed from routine clinical prostate biopsy whole-slide images (WSIs), and a conditional generative adversarial network (cGAN) was trained to synthesize PIN-4 staining patterns directly from native H&E image patches. The final dataset comprised 172 paired WSIs from 93 patients and 27,298 registered 1024x1024 patch pairs, spanning adenocarcinoma-positive and benign cases with representation across age, race, and ethnicity groups. The model was evaluated on a held-out test set of 1,814 patch pairs from 17 WSIs, achieving a mean peak signal-to-noise ratio (PSNR) of 21.88 dB, structural similarity index measure (SSIM) of 0.667, Pearson correlation coefficient (PCC) of 0.684, and learned perceptual image patch similarity (LPIPS) of 0.417. Qualitative review by a board-certified pathologist showed that generated images captured diagnostically relevant PIN-4 staining patterns, including AMACR/racemase expression and basal-cell-associated staining, while preserving spatial correspondence with the source H&E morphology. Accuracy of synthesis varied across morphologically complex regions, including high-grade carcinoma and intraductal carcinoma. These results support the feasibility of supervised PIN-4 synthesis from routinely acquired brightfield H&E prostate biopsy images. The approach enables direct interpretation of predicted PIN-4 marker patterns in the context of the source prostate H&E architecture, addressing a current spatial limitation of conventional adjacent-section IHC.
Computed tomography (CT) is indispensable for clinical diagnosis and image-guided interventions but exposes patients to ionizing radiation, motivating the development of safer imaging alternatives. Ultrasound (US) is non-ionizing and widely accessible; however, it is highly operator dependent and lacks quantitative tissue characterization, often leading to diagnostic uncertainty and unnecessary CT examinations. This work presents a 3D ultrasound-derived pseudo-CT (UD-pCT) framework that generates CT-like anatomical reference volumes inferred from US, without aiming to reproduce physically accurate Hounsfield Units. Paired 3D kidney US and CT volumes from the TRUSTED dataset are first spatially aligned using a landmark-based multimodal registration pipeline, creating high-quality paired inputs for supervised training of an adversarial framework. The proposed Bottleneck Transformer Residual U-Net3D (BT-ResUNet3D) model employs a 3D residual encoder-decoder generator augmented with a transformer bottleneck, enabling effective modeling of fine-grained local anatomical structures as well as long-range volumetric dependencies, while a 3D Conditional PatchGAN discriminator enforces local structural realism in the synthesized pseudo-CT volumes. Quantitative evaluation using PSNR and SSIM demonstrates that the proposed method outperforms established baselines in structural fidelity and perceptual image quality. The UD-pCT volumes provide real-time anatomical reference for operator guidance, potentially reducing acquisition variability and unnecessary CT use. A limitation of this study is the relatively small paired dataset, which may limit the generalizability of the proposed model.